Mast cells induce epithelial-to-mesenchymal transition and migration in non-small cell lung cancer through IL-8/Wnt/β-catenin pathway.

Abstract:

:Background: In the various cancer, mast cells (MCs) infiltration is correlated with a worse prognosis. There is an increasing evidence that MCs and their mediators are participated in remodeling of the tumor microenvironment and facilitate tumor growth, epithelial-to-mesenchymal transition (EMT) and metastasis. Methods: The transwell was conducted to evaluate the correlations between MCs and non-small cell lung cancer (NSCLC) cells in vitro. The RNA interference of β-catenin was performed to further explore the signaling pathway. Lung adenocarcinoma cell line A549 and human MC (HMC-1) were subcutaneously injected into BALB/c nude mice. The conventional experiment methods (such as quantitative RT-PCR Western Blot, Immunofluorescence, and ELISA) were used in the present study. Results: We found that high density of MCs in NSCLC correlates with worse prognosis. The NSCLC cells could release CCL5 and recruit MCs to the tumor microenvironment. Then, we explored that HMC-1 transplantation accelerated the growth of A549 cell in nude mice. Moreover, the MCs-derived factors were responsible for tumor growth. When NSCLC cells were activated, MCs produced various factors that induced EMT and migration. We also identified that CXCL8/interleukin (IL)-8 served as the major modulator containing in the activated MC conditioned medium. Furthermore, MCs and exogenous IL-8 promoted β-catenin phosphorylation in NSCLC cells. Inhibiting the Wnt/β-catenin pathway by RNA interference could revert EMT and migration of NSCLC. Conclusions: Our study suggests that MCs are recruited into NSCLC microenvironment and improve the EMT and migration of cancer cells, thereby accelerating the growth of NSCLC.

journal_name

J Cancer

journal_title

Journal of Cancer

authors

Qu J,Cheng T,Liu L,Heng J,Liu X,Sun Z,Wang W,Li K,Yang N

doi

10.7150/jca.29953

subject

Has Abstract

pub_date

2019-06-09 00:00:00

pages

3830-3841

issue

16

issn

1837-9664

pii

jcav10p3830

journal_volume

10

pub_type

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